François Simon

Publications (77)378.98 Total impact

• Article: Hepatitis B Virus Exposure during Childhood in Cameroon, Central African Republic and Senegal Following the Integration of HBV Vaccine in the Expanded Program on Immunization.

  Marie-Anne Rey-Cuille, Richard Njouom, Claudine Bekondi, Abdoulaye Seck, Chrysostome Gody, Petulla Bata, Benoit Garin, Sarah Maylin, Loic Chartier, François Simon, Muriel Vray
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  ABSTRACT: BACKGROUND:: More than 2 billion people worldwide have been exposed to Hepatitis B Virus (HBV). To prevent these infections, Senegal and Cameroon integrated the HBV vaccine into their Expanded Programs on Immunization (EPI) in 2005, as did the Central African Republic (CAR) in 2008. We evaluated the prevalence of HBV exposure and infection following the integration of the HBV vaccine in the EPI. METHODS:: An observational cross-sectional study was conducted among hospitalized children aged 3 months to 6 years in Cameroon, CAR and Senegal. Plasma was collected for the detection of anti-HBc, anti-HBs, and HBsAg in children anti-HBc+anti-HBs-. RESULTS:: Between April 2009 and May 2010, 1783 children were enrolled, 19.4% of whom were anti-HBc-positive. The percentage of children with anti-HBc was 44.4% among the children younger than 6 months old, decreasing after 6 months to reach 18.8% at 12 months old. This decline was followed by a rapid increase in anti-HBc positivity rate in CAR observed as early as 12 months of age compared to Cameroon and Senegal where the anti HBc increased between the age of 18 months and 36 months, respectively. Prevalence of HBsAg-positive children was significantly higher in CAR than in Cameroon and Senegal (5.1% versus 0.7% and 0.2%), (p<0.001). Socio-economical level, age and country were factors associated with the presence of anti-HBc. CONCLUSION:: Passive transfer of anti-HBC maternal antibodies versus HBV exposure could be differentiated as early as 12 months of age. The low prevalence of anti-HBc and HBsAg among children born after the integration of HBV vaccine in the EPI in Cameroon and Senegal, suggests a positive impact of HBV vaccination.
  The Pediatric Infectious Disease Journal 05/2013; · 3.58 Impact Factor
• Article: High level of susceptibility to human TRIM5alpha conferred by HIV-2 capsid sequences.

  Junko S Takeuchi, Benjamin Perche, Julie Migraine, Séverine Mercier-Delarue, Diane Ponscarme, François Simon, François Clavel, Béatrice Labrosse
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  ABSTRACT: BACKGROUND: HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity. We have tested the possibility that a greater susceptibility of HIV-2 capsid (CA) to the human restriction factor TRIM5alpha (hTRIM5alpha) could contribute to these differences. RESULTS: We constructed recombinant clones expressing CA from a variety of HIV-2 viruses in the context of HIV-1 NL4-3-luciferase. CA sequences were amplified from the plasma of HIV-2 infected patients, including 8 subtype A and 7 subtype B viruses. CA from 6 non-epidemic HIV-2 subtypes, 3 HIV-2 CRF01_AB recombinants and 4 SIVsmm viruses were also tested. Susceptibility to hTRIM5alpha was measured by comparing single-cycle infectivity in human target cells expressing hTRIM5alpha to that measured in cells in which hTRIM5alpha activity was inhibited by overexpression of hTRIM5gamma.The insertion of HIV-2 CA sequences in the context of HIV-1 did not affect expression and maturation of the HIV-2 CA protein. The level of susceptibility hTRIM5alpha expressed by viruses carrying HIV-2 CA sequences was up to 9-fold higher than that of HIV-1 NL4-3 and markedly higher than a panel of primary HIV-1 CA sequences. This phenotype was found both for viruses carrying CA from primary HIV-2 sequences and viruses carrying CA from laboratory-adapted HIV-2 clones. High hTRIM5alpha susceptibility was found in all HIV-2 subtypes. In this series of viruses, susceptibility to hTRIM5alpha was not significantly affected by the presence of a proline at position 119 or by the number of prolines at positions 119, 159 or 178 in HIV-2 CA. No significant correlation was found between HIV-2 viremia and sensitivity to hTRIM5alpha. CONCLUSIONS: HIV-2 capsid sequences expressed high levels of susceptibility to hTRIM5alpha. This property, common to all HIV-2 sequences tested, may contribute in part to the lower replication and pathogenicity of this virus in humans.
  Retrovirology 05/2013; 10(1):50. · 6.47 Impact Factor
• Article: Fully automated quantification of cytomegalovirus (CMV) in whole blood with the new sensitive Abbott RealTime CMV assay in the era of the CMV international standard.

  Nathalie Schnepf, Catherine Scieux, Matthieu Resche-Riggon, Linda Feghoul, Alienor Xhaard, Sébastien Gallien, Jean-Michel Molina, Gérard Socié, Denis Viglietti, François Simon, Marie-Christine Mazeron, Jérôme Legoff
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  ABSTRACT: Fully standardized reproducible and sensitive quantification assays for cytomegalovirus (CMV) are needed to better define thresholds for antiviral therapy initiation and interruption. We evaluated the new released Abbott RealTime CMV assay for CMV quantification on whole blood (WB) that includes automated extraction and amplification (m2000 RealTime system). Sensitivity, accuracy, linearity and intra- and inter-assay variability were validated in WB matrix using quality control panels (QCMD) and the WHO international standard (IS). Intra- and inter-assay coefficients of variation were 1.37% and 2.09% at 5 log10 copies/ml and 2.41% and 3.80% at 3 log10 copies/ml, respectively. According to QCMD and Abbott RealTime CMV expected values, the lower limit of quantification was 104 and below 50 copies/ml, respectively. The conversion factor between international units and copies (2.18), determined from serial dilutions of the WHO IS in WB, was significantly different from the factor provided by the manufacturer (1.56) (P = 0.001). Results from 302 clinical samples were compared to the Qiagen/artus CMV assay on the same m2000 RealTime system. The two assays provided highly concordant results (concordance correlation coefficient = 0.92), but Abbott RealTime CMV assay detected and quantified respectively 20.6% and 47.8% more samples than Qiagen/artus CMV assay. The sensitivity and reproducibility results along with automation fulfill quality requirements to implement Abbott RealTime CMV assay in clinical settings. Our results stress out the need for careful validation of conversion factors of the WHO IS in WB provided by manufacturers to allow future comparison of results obtained with different assays.
  Journal of clinical microbiology 04/2013; · 4.16 Impact Factor
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  Available from: Fabien Lavocat

  Article: Quantification of hepatitis B e antigen between Elecsys HBeAg and Architect HBeAg assays among patients infected with hepatitis B virus.

  Sarah Maylin, Anders Boyd, Michelle Martinot-Peignoux, Constance Delaugerre, Georges Bagnard, Martine Lapalus, Fabien Zoulim, Fabien Lavocat, Patrick Marcellin, François Simon, Pierre-Marie Girard, Karine Lacombe
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  ABSTRACT: BACKGROUND: Among patients infected with hepatitis B virus (HBV), quantification of hepatitis B e antigen (HBeAg) is accruing substantial clinical relevance as a marker for HBeAg-loss during treatment. No direct comparison has been made between assays that quantify HBeAg. OBJECTIVES: To compare the performance of HBeAg quantification (qHBeAg) between Architect and Elecsys HBeAg assays among 183 patients with chronic HBV infection (94 treatment-naïve HBV-monoinfected and 89 antiretroviral-experienced HIV-HBV co-infected). STUDY DESIGN: qHBeAg was determined in Paul Erlich Institute Units (PEIU)/mL using previously designed protocols. Values were compared with correlation and linear regression. Bland-Altman analysis was used to compare mean differences (d¯) between Elecsys and Architect assays and limits of agreement (LOA) (±2 standard deviations [SD]). RESULTS: Between-assay correlation was significant overall (r=0.970), yet stronger for qHBeAg<1000 (n=131) versus >1000PEIU/mL (n=52) as determined by the Elecsys assay (r=0.969 vs. 0.880, respectively). On average, the Elecsys assay reported qHBeAg at 13.3PEIU/mL lower than the Architect assay (LOA: -415.9, 389.3), while LOA between assays were much wider at higher levels (<1000: -198.2, 147.9; ≥1000PEIU/mL: -688.4, 721.5). Further analysis indicated that d¯ did not change substantially with respect to HBV genotype, precore mutation, and CD4+ cell count, regardless of HBeAg-level. Nevertheless, seven of eight patients with highly divergent between-assay results had HBV-DNA>2000IU/mL. CONCLUSIONS: Elecsys and Architect assays report similar qHBeAg units with high correlation. Since qHBeAg was performed using an in-house approach, a commercially-available assay could reduce between-assay discrepancies, especially at higher HBeAg-levels.
  Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2013; · 3.12 Impact Factor
• Article: Cross-group neutralization of HIV-1 and evidence for conservation of the PG9/PG16 epitopes within divergent groups.

  Martine Braibant, Eun-Yeung Gong, Jean-Christophe Plantier, Thierry Moreau, Elodie Alessandri, François Simon, Francis Barin
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  ABSTRACT: OBJECTIVE:: HIV-1 has been classified into 4 groups: M, N, O and P. The aim of this study was to revisit the cross-group neutralization using a highly diverse panel of primary isolates (PI). DESIGN:: The panel of viruses included 9 HIV-1 group O PIs, 1 recombinant M/O PI, 1 group N PI, 1 group P PI, 2 group M (subtype B) PIs and the HIV-1 group M adapted strain MN. METHODS:: All the viruses were tested for neutralization in TZM-bl cells, using sera issued from patients infected by viruses of group M (n = 11), O (n = 12) and P (n = 1), and a panel of nine human monoclonal broadly neutralizing antibodies (HuMo bNAbs). RESULTS:: Although the PIs displayed a wide spectrum of sensitivity to neutralization by the human sera, cross-group neutralization was clearly observed. In contrast, the bNAbs did not show any cross-group neutralization, except PG9 and PG16. Interestingly, the group N prototype strain YBF30 was highly sensitive to neutralization by PG9 (IC50: 0.28 μg/mL) and PG16 (IC50: < 0.12 μg/mL). The interaction between PG9 and key residues of YBF30 was confirmed by molecular modeling. CONCLUSIONS:: The conservation of the PG9 and PG16 epitopes within groups M and N provides an argument for their relevance as components of a potentially efficient HIV vaccine immunogen.
  AIDS (London, England) 01/2013; · 4.91 Impact Factor
• Article: Prevalence of antibodies and RNA genome of hepatitis E virus in a cohort of French immunocompromised.

  Sarah Maylin, Robin Stephan, Jean-Michel Molina, Marie-Noelle Peraldi, Catherine Scieux, Elisabeth Nicand, François Simon, Constance Delaugerre
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  ABSTRACT: Recently, cases of chronic hepatitis E have been identified in immunocompromised patients. To evaluate the prevalence of anti-HEV IgG antibodies and the persistence of HEV-RNA in sera of immunocompromised patients with regular follow-up at Saint-Louis Hospital in Paris, France. 307 samples collected from 261 HIV-infected patients and 46 kidney transplant (KT)-patients were retrospectively tested for the presence of the following hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index, and HEV-RNA. Anti-HEV IgG positive serology was found in 4 HIV-infected patients (1.5%) and 3 KT-patients (6.5%), leading to an overall seroprevalence of 2.3%. HEV-RNA detection was not observed among 55 HIV-patients at higher risk of chronic HEV (<200 CD4 cells/mm(3), elevated alanine aminotransferase (ALT) levels, and/or positive anti-HEV antibodies) and among 44 KT-patients. None of the seven patients had anti-HEV IgM antibodies, thereby excluding any acute infection. The IgG avidity index confirmed past HEV infection among tested patients. The low seroprevalence observed in the Paris region does not warrant a systematic evaluation of HEV infection in immunocompromised patients. However, HEV infection must be examined as a possibility if unexplained increases in ALT should occur and after more common viral hepatitis infections are excluded.
  Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2012; 53(4):346-9. · 3.12 Impact Factor
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  Available from: dx.plos.org

  Article: I223R mutation in influenza A(H1N1)pdm09 neuraminidase confers reduced susceptibility to oseltamivir and zanamivir and enhanced resistance with H275Y.

  Jérome LeGoff, Dominique Rousset, Georges Abou-Jaoudé, Anne Scemla, Patricia Ribaud, Séverine Mercier-Delarue, Valérie Caro, Vincent Enouf, François Simon, Jean-Michel Molina, Sylvie van der Werf
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  ABSTRACT: Resistance of pandemic A(H1N1)2009 (H1N1pdm09) virus to neuraminidase inhibitors (NAIs) has remained limited. A new mutation I223R in the neuraminidase (NA) of H1N1pdm09 virus has been reported along with H275Y in immunocompromised patients. The aim of this study was to determine the impact of I223R on oseltamivir and zanamivir susceptibility. The NA enzymatic characteristics and susceptibility to NAIs of viruses harbouring the mutations I223R and H275Y alone or in combination were analyzed on viruses produced by reverse genetics and on clinical isolates collected from an immunocompromised patient with sustained influenza H1N1pdm09 virus shedding and treated by oseltamivir (days 0-15) and zanamivir (days 15-25 and 70-80). Compared with the wild type, the NA of recombinant viruses and clinical isolates with H275Y or I223R mutations had about two-fold reduced affinity for the substrate. The H275Y and I223R isolates showed decreased susceptibility to oseltamivir (246-fold) and oseltamivir and zanamivir (8.9- and 4.9-fold), respectively. Reverse genetics assays confirmed these results and further showed that the double mutation H275Y and I223R conferred enhanced levels of resistance to oseltamivir and zanamivir (6195- and 15.2-fold). In the patient, six days after initiation of oseltamivir therapy, the mutation H275Y conferring oseltamivir resistance and the I223R mutation were detected in the NA. Mutations were detected concomitantly from day 6-69 but molecular cloning did not show any variant harbouring both mutations. Despite cessation of NAI treatment, the mutation I223R persisted along with additional mutations in the NA and the hemagglutinin. Reduced susceptibility to both oseltamivir and zanamivir was conferred by the I223R mutation which potentiated resistance to both NAIs when associated with the H275Y mutation in the NA. Concomitant emergence of the I223R and H275Y mutations under oseltamivir treatment underlines the importance of close monitoring of treated patients especially those immunocompromised.
  PLoS ONE 01/2012; 7(8):e37095. · 4.09 Impact Factor
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  Available from: Dominique Rousset

  Article: Low immune response to hepatitis B vaccine among children in Dakar, Senegal.

  Marie-Anne Rey-Cuille, Abdoulaye Seck, Richard Njouom, Loïc Chartier, Housseyn Dembel Sow, Mamadou, Amadou Sidy Ka, Mohamadou Njankouo, Dominique Rousset, Tamara Giles-Vernick, Guillemette Unal, Jean-Marie Sire, Benoît Garin, François Simon, Muriel Vray
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  ABSTRACT: HBV vaccine was introduced into the Expanded Programme on Immunization (EPI) in Senegal and Cameroon in 2005. We conducted a cross-sectional study in both countries to assess the HBV immune protection among children. All consecutive children under 4 years old, hospitalized for any reason between May 2009 and May 2010, with an immunisation card and a complete HBV vaccination, were tested for anti-HBs and anti-HBc. A total of 242 anti-HBc-negative children (128 in Cameroon and 114 in Senegal) were considered in the analysis. The prevalence of children with anti-HBs ≥ 10 IU/L was higher in Cameroon with 92% (95% CI: 87%-97%) compared to Senegal with 58% (95% CI: 49%-67%), (p<0.001). The response to vaccination in Senegal was lower in 2006-2007 (43%) than in 2008-2009 (65%), (p = 0.028). Our results, although not based on a representative sample of Senegalese or Cameroonian child populations, reveal a significant problem in vaccine response in Senegal. This response problem extends well beyond hepatitis B: the same children who have not developed an immune response to the HBV vaccine are also at risk for diphtheria, tetanus, pertussis (DTwP) and Haemophilus influenzae type b (Hib). Field biological monitoring should be carried out regularly in resource-poor countries to check quality of the vaccine administered.
  PLoS ONE 01/2012; 7(5):e38153. · 4.09 Impact Factor
• Article: Comparison between Elecsys HBsAg II and architect HBsAg QT assays for quantification of hepatitis B surface antigen among patients coinfected with HIV and hepatitis B virus.

  Sarah Maylin, Anders Boyd, Constance Delaugerre, Fabien Zoulim, Fabien Lavocat, François Simon, Pierre-Marie Girard, Karine Lacombe
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  ABSTRACT: Hepatitis B surface antigen (HBsAg) quantification has been steadily gaining interest as a clinical marker of therapeutic efficacy, for which two commercial assays are currently available: Architect HBsAg QT (Architect) and Elecsys HBsAg II (Elecsys). HBsAg quantification was evaluated using both assays in 126 human immunodeficiency virus (HIV) and hepatitis B virus (HBV)-coinfected patients initiating treatment with tenofovir dipivoxil fumarate. Linear regression and correlation were used to establish the relationship between the two methods. Bland-Altman analysis was performed to determine mean between-assay difference and limits of agreement (LOA) (±2 standard deviations [SD]) both overall and stratified on HBV (hepatitis B envelope antigen [HBeAg] status, replication, genotype, HBV mutants) or HIV (CD4(+) cell count) cofactors. There was a significant correlation between Elecsys and Architect assays (correlation coefficient, r = 0.959; P < 0.001). HBsAg quantification using the Elecsys assay was on average 0.200 log(10) IU/ml (LOA, -0.500, 0.800) higher than that using Architect, which was consistent across levels of CD4(+) cell count, presence of precore and YMDD mutations, and HBeAg status. A slightly larger mean between-assay difference was observed with genotypes A and G (0.196 and 0.201, respectively) versus HBV genotypes D and E (0.036 and 0.030, respectively). Mutations on the S region at position s120/s145 were the only determinant in which the mean between-assay difference in HBsAg quantification was lower than the null value (-0.078). In conclusion, the Elecsys assay, with automatic on-board dilution, is capable of quantifying serum HBsAg levels in HIV-HBV-coinfected patients, with very high correlation with the Architect assay.
  Clinical and vaccine immunology: CVI 12/2011; 19(2):242-8. · 2.37 Impact Factor
• Article: HIV-1 group N: travelling beyond Cameroon.

  Constance Delaugerre, Fabienne De Oliveira, Caroline Lascoux-Combe, Jean-Christophe Plantier, François Simon
  The Lancet 11/2011; 378(9806):1894. · 38.28 Impact Factor
• Article: Pandemic Influenza A (H1N1) Infection among HIV-Infected Adults in France.

  Mathieu Tourdjman, Sokéo Chea, Jérome Le Goff, Nathalie Colin De Verdiere, Anne Scemla, Juliette Pavie, François Simon, Jean-Michel Molina
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  ABSTRACT: Clinical, biological, and radiological findings of influenza A (H1N1)-confirmed cases among HIV-infected patients presenting in a French university hospital between October 2009 and January 2010 were systematically reviewed. No severe influenza infection was observed, but a high frequency of secondary bacterial pneumonia is reported among pneumococcal unvaccinated patients.
  Journal of the International Association of Physicians in AIDS Care (JIAPAC) 05/2011; 10(4):229-31.
• Article: Comparative RNA quantification of HIV-1 group M and non-M with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 v2.0 and Abbott Real-Time HIV-1 PCR assays.

  Jean-Marie Sire, Muriel Vray, Mourad Merzouk, Jean-Christophe Plantier, Juliette Pavie, Sarah Maylin, Julie Timsit, Caroline Lascoux-Combe, Jean-Michel Molina, François Simon, Constance Delaugerre
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  ABSTRACT: A new version of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 assay (CA/CTM v2.0) has been introduced to overcome the underquantification observed with the first version. We compared the Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays for HIV-1 group M and non-M viral load measurement. We found a good correlation (r = 0.96) between the 2 techniques for the 260 HIV-1 group M plasma samples tested. The Roche Cobas assay gave significantly higher values than the Abbott assay, and 51 samples (20%) yielded differences greater than 0.5 log10 copies per milliliter. Conversely, 2 samples were more than 0.5 log10 copies per milliliter higher with the Abbott assay than with the Roche Cobas assay. Among the 84 samples with undetectable viral load in the Abbott assay (detection limit 40 copies/mL), 17 (20%) were detectable with the CA/CTM v2.0 assay (detection limit 20 copies/mL), with values ranging from 41 to 897 copies per milliliter. Extrapolation of the Abbott curves led to 10/17 (59%) of these samples being quantifiable. HIV-1 groups O and P were similarly quantified by the two techniques. The results of the Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays correlate well. The new version of the CA/CTM assay shows improved sensitivity. Nevertheless, the 2 assays differ by more than 0.5 log₁₀ copies per milliliter for some samples.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2011; 56(3):239-43. · 4.43 Impact Factor
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  Available from: Damien Roux

  Article: JC virus variant associated with cerebellar atrophy in a patient with AIDS.

  Damien Roux, Marie-Anne Bouldouyre, Séverine Mercier-Delarue, Danielle Seilhean, Anne-Marie Zagdanski, Constance Delaugerre, François Simon, Jean-Michel Molina, Jerôme Legoff
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  ABSTRACT: The human polyomavirus JC virus (JCV) is the agent of progressive multifocal leukoencephalopathy (PML). It has also recently been involved in cerebellar atrophy. Factors involved in this entity are elusive. We present a case of a human immunodeficiency virus (HIV)-infected patient with PML and cerebellar atrophy. In addition to a compartmentalization of JCV strains between urine, cerebrospinal fluid, and cerebellum, specific rearrangements in the JCV regulatory region were observed in the cerebellum, resulting in alterations of transcription factor binding sites. Our data underline the importance of searching for JCV in HIV-infected patients with cerebellar disorders and suggest that mutations in the regulatory region may be involved in cerebellar degeneration.
  Journal of clinical microbiology 03/2011; 49(6):2196-9. · 4.16 Impact Factor
• Article: Impact of HIV-1 group O genetic diversity on genotypic resistance interpretation by algorithms designed for HIV-1 group M.

  Agnès Depatureaux, Charlotte Charpentier, Marie Leoz, Guillemette Unal, Florence Damond, Anfunbom Kfutwah, Aurélia Vessière, François Simon, Jean-Christophe Plantier
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  ABSTRACT: HIV-1 group O (HIV-O) is characterized by a high genetic divergence from HIV-1 group M viruses. Little is known about the therapeutic impact of this diversity. The aim of this study was to assess in a large series of samples (1) the genotypic impact of natural polymorphism of the HIV-O reverse transcriptase and protease genes; and (2) the predictive value of resistance interpretation algorithms developed for HIV-1 group M when used for highly mutated HIV-O viruses. Sixty-eight antiretroviral-naive and 9 highly antiretroviral-experienced HIV-O-infected patients were included. The viruses were sequenced and resistance-associated mutations were identified using 3 different algorithms (Agence Nationale de Recherches sur le SIDA et les hépatites virales, Rega, Stanford). All HIV-O samples naturally exhibited the A98G and V179E resistance mutations in the reverse transcriptase region; 54% of samples presented the Y181C mutation, conferring resistance to nonnucleoside reverse transcriptase inhibitors. Twelve minor resistance mutations, present in more than 75% of the protease sequences, led to the different algorithms giving discrepant results for nelfinavir and saquinavir susceptibility. A marked virological response was observed in 8 of the 9 antiretroviral-experienced patients, despite the prediction of limited activity of the combination for 5 to 8 patients according to the algorithm used. The high level of natural polymorphism in HIV-O genes, and the important discrepancies between genotypic resistance interpretation and the virological response, emphasize the need for resistance algorithm rules better adapted to HIV-O.
  JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2011; 56(2):139-45. · 4.43 Impact Factor
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  Available from: PubMed Central

  Article: Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load.

  Papa Saliou Mbaye, Anna Sarr, Jean-Marie Sire, Marie-Louise Evra, Adama Ba, Jean Daveiga, Aboubakry Diallo, Fatou Fall, Loic Chartier, François Simon, Muriel Vray
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  ABSTRACT: Despite the high prevalence of chronic hepatitis B (CHB) in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM) and two biochemical scores (FibroTest®, Fibrometer®) to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10) IU/mL and normal alanine aminotransferase (ALT) values. LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB). Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring. 225 patients were evaluated (84% male) and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT), and Fibrometer® (FM) using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis) and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively. In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.
  PLoS ONE 01/2011; 6(7):e22291. · 4.09 Impact Factor
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  Available from: PubMed Central

  Article: High burden of non-influenza viruses in influenza-like illness in the early weeks of H1N1v epidemic in France.

  Nathalie Schnepf, Matthieu Resche-Rigon, Antoine Chaillon, Anne Scemla, Guillaume Gras, Oren Semoun, Pierre Taboulet, Jean-Michel Molina, François Simon, Alain Goudeau, Jérôme LeGoff
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  ABSTRACT: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.
  PLoS ONE 01/2011; 6(8):e23514. · 4.09 Impact Factor
• Article: Microarray for hepatitis B virus genotyping and detection of 994 mutations along the genome.

  Marie Gauthier, Bertrand Bonnaud, Maud Arsac, Fabien Lavocat, Jérôme Maisetti, Alan Kay, François Simon, Fabien Zoulim, Guy Vernet
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  ABSTRACT: Genome analysis of hepatitis B virus (HBV) in patient sera is helpful for monitoring treatment. We developed an improved version of a DNA microarray to identify HBV genotypes and to detect mutations of interest in the S, Pol, Core, and X genes. It includes an automated software analysis of fluorescence values for simpler, more robust data interpretation. In this version, probes were added to identify genotype H, to analyze 155 additional positions, and to detect 561 additional polymorphisms. Sequences were added to the alignments to resolve hybridization problems due to natural polymorphisms in the vicinity of important codons. The duplex PCR protocol allowed whole-genome analysis in a single tube. An alternative nested-PCR protocol allowed genotyping and mutations in S and reverse transcriptase (rt) genes in patients with low viral loads, as demonstrated in patients with less than 400 HBV genome copies/ml. Reproducibility was high, with variation coefficients lower than 3%. Only 0.57% of 20,771 codons from 253 samples could not be identified. The concordance with Sanger sequencing for the identification of codons improved from 92.8% to 95.7% with the improved version. Concordance was higher than 91% for codons associated with resistance to lamivudine, emtricitabine, telbivudine, famciclovir, entecavir, and tenofovir with vaccine escape and for pre-Core mutants. Concordance was lower for adefovir resistance mutations (68.6%) and mutations in the basal core promoter (60.3%), probably because hybridization efficiency was affected by the low GC content of the probes. A concordance of 93.7% with sequencing for genotype identification was observed in 190 specimens, lower than that obtained with the first version, possibly due to mixed virus populations.
  Journal of clinical microbiology 11/2010; 48(11):4207-15. · 4.16 Impact Factor
• Article: Four year follow-up of simplification therapy with once-daily emtricitabine, didanosine and efavirenz in HIV-infected patients (ALIZE ANRS 099 trial).

  Sébastien Gallien, Valérie Journot, Willy Rozenbaum, Patrick Yéni, Philippe Morlat, Isabelle Poizot-Martin, Jacques Reynes, Véronique Reliquet, Pascale Leclercq, François Simon, Geneviève Chêne, Jean-Michel Molina
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  ABSTRACT: once-daily combinations of efavirenz and two nucleoside analogues are recommended for the treatment of HIV infection. Long-term efficacy and safety data are scarce for the combination of efavirenz, emtricitabine and didanosine. the ALIZE ANRS 099 trial enrolled 355 adults with plasma HIV RNA levels of <400 copies/mL under a protease inhibitor-based regimen, who were randomized to remain on this regimen or to switch to a once-daily regimen of emtricitabine, didanosine and efavirenz for 48 weeks. An extended 4 year follow-up was available for the 178 patients who switched to the efavirenz-containing regimen, and assessed plasma HIV RNA levels, CD4 cell counts, safety and tolerability. after a median follow-up of 42 months, 121 patients (68%) remained on an efavirenz-based regimen, and 62% and 57% had plasma HIV RNA levels of <400 and <50 copies/mL, respectively, in an intent-to-continue analysis with missing data and treatment discontinuation considered as failure. There was a significant increase in CD4 cell count of 41 cells/mm(3). Drug-related adverse events were the main reason for treatment discontinuation in 26 patients (15%), and 15 were reported during the first year of therapy (58%). There was no emergence of clinically defined lipodystrophy, and lipid and glucose profiles were favourable with a significant increase from baseline of high-density lipoprotein cholesterol levels (median increase 12 mg/dL, P < 10(-4)). a once-daily regimen of emtricitabine, didanosine and efavirenz provided a durable antiretroviral response and was well tolerated through 4 years of therapy.
  Journal of Antimicrobial Chemotherapy 10/2010; 66(1):184-91. · 5.07 Impact Factor
• Article: Time course of total HIV-1 DNA and 2-long-terminal repeat circles in patients with controlled plasma viremia switching to a raltegravir-containing regimen.

  Constance Delaugerre, Isabelle Charreau, Josephine Braun, Marie-Laure Néré, Nathalie de Castro, Patrick Yeni, Jade Ghosn, Jean-Pierre Aboulker, Jean-Michel Molina, François Simon
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  ABSTRACT: Early integration of HIV proviral DNA into the host cell genome prevents viral eradication, despite suppressive HAART. In vitro, integrase inhibitors reduce proviral DNA levels and rapidly increase 2-long-terminal repeat (LTR) circle levels. We examined the effect of raltegravir on the time course of HIV-1 DNA forms in patients with controlled viremia. The EASIER-ANRS 138 randomized trial demonstrated that switching from enfuvirtide to raltegravir maintained virological suppression in treatment-experienced patients with viral load below 400 copies/ml. We analyzed total HIV-1 DNA and 2-LTR circle levels measured at weeks (W)0 and 24 in the first 30 patients enrolled in each arm, and at W48 in the raltegravir arm. At W0 the total DNA level was 3.6 log(10)/10(6) peripheral blood mononuclear cell (PBMC) in both groups, and 2-LTR circles were detected in six patients (median 89 copies/10(6) PBMC). At W24 the total DNA level was 3.6 log(10)/10(6) PBMC in both groups, and 2-LTR circles were detected in three new patients. At W48 the total HIV DNA level in the raltegravir group was 3.5 log(10)/10(6) PBMC, and 2-LTR circles were undetectable. No significant change in total HIV DNA occurred between W0 and W24 in either arm (P = 0.71) and no significant change was observed in the raltegravir arm at W48. In most patients on effective HAART, including regimens containing an integrase inhibitor, the viral reservoir, reflected by the HIV-1 DNA load, is stable and nondynamic during the 48 weeks of follow-up.
  AIDS (London, England) 09/2010; 24(15):2391-5. · 4.91 Impact Factor
• Article: Case report: Cure of chronic infection with hepatitis C virus after 6 weeks of peg-interferon and ribavirin in a patient co-infected with HIV.

  Anne Rachline, Pierre Palmer, François Simon, Jean-Michel Molina
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  ABSTRACT: The recommended treatment duration of chronic hepatitis C virus (HCV) in patients infected with human immunodeficiency virus (HIV) is 48 weeks. This report describes a patient co-infected with HCV genotype 2 and HIV who discontinued HCV therapy after 6 weeks because of adverse events and had a sustained virologic response.
  Journal of Medical Virology 07/2010; 82(7):1150-1. · 2.82 Impact Factor